Copd lecture notes
- 1. , COPD: CPT 1 UTECH Dr E. Watson PharmD.
- 2. Learning Objectives : upon completion of this lecture, the student should be able to Define the two major forms of chronic obstructive COPD. Be familiar with The Global initiative for Chronic Obstructive Lung Disease (GOLD) definition of COPD. Ref: http://www.goldcopd.org. List the risk factors associated with COPD. Describe the pathophysiology of COPD.
- 3. Learning Objectives Cont’d. Describe the signs and symptoms of COPD. Differentiate between chronic bronchitis and emphysema. Describe the non-pharmacologic and pharmacologic management of COPD. To identify the role of the pharmacist in the management of COPD.
- 4. Key Points COPD is a preventable and treatable disease with significant extra-pulmonary effects that may contribute to severity in individual patients. The airflow limitation is generally not reversible and is progressive. The most common risk factor worldwide is cigarette smoking. Smoking cessation is to be offered to all patients still smoking.
- 5. Key Points cont’d. Consider a diagnosis of COPD for any patient with dyspnea, chronic cough and exposure to risk factors. Confirm with spirometry. Four components to the management; assess and monitor, reduce risk factors, manage stable COPD and manage exacerbations.
- 6. Key Points cont’d. Pharmacotherapy aims at prevention and control of symptoms, reduce frequency and severity of exacerbations, improve QOL and improve exercise tolerance. Patient education is an important part of therapy. Thus the pharmacist is integral to the management. COPD is often associated with exacerbation of symptoms.
- 7. Definition: National Heart, Lung and Blood institute (NHLBI) and WHO COPD is a group of chronic respiratory disorders that lead to progressive tissue degeneration and obstruction in the airways and lungs that is not fully reversible. They are debilitating conditions that affect the individual’s ability to work and function independently. These include; Chronic bronchitis , asthmatic bronchitis and emphysema . May coexist. COPD may coexist with asthma.
- 8. Definition: GOLD COPD is a preventable and treatable disease with significant extra-pulmonary effects that may contribute to severity in individual patients. Its pulmonary component is characterized by airflow limitation that is non-reversible. The airflow resistance is normally progressive and is associated with an abnormal inflammatory response of the lung to noxious particles or gas. The GOLD definition does not use the term bronchitis or emphysema and excludes asthma (reversible air flow limitation)
- 9. Chronic Bronchitis Recurrent excessive mucus secretion into the bronchial tree resulting in airway obstruction due to edema and bronchial inflammation. Patient has a cough producing more than 30ml of sputum in 24hrs for at least 3 months of the year, for 2 consecutive years. Sputum is thick and obstructs airflow.
- 10. Emphysema A condition of the lung characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without any obvious fibrosis. There is a lack of uniformity in airspace enlargement, resulting in loss of alveolar surface areas.
- 11. Emphysema It causes destruction of the alveolar walls and capillaries by increased lung enzymatic activity. May include; centricinar, panacinar and distal acinar.
- 12. Chronic Asthma Characterized by recurrent, (intermittent) reversible bronchspasms. Reversibility may be spontaneous or after drugs therapy. Airway inflammation and hyper-responsiveness to a variety of stimuli are important components of asthma.
- 13. Risk factors: Major Worldwide cigarette smoking is the most common encountered risk. The best documented genetic risk factor is a severe alpha 1 trypsin deficiency. Occupational hazards and indoor pollution (biogas burning). Age. Male gender. Existing impaired lung function.
- 14. Risk factors: Minor Air pollution. Alcohol. Race. Nutritional status. Family history. Bronchial reactivity.
- 15. Pathophysiology; Chronic Bronchitis Inhalation of noxious particles and gases stimulates the activation of neutrophils, macrophages and CD8+ lymphocytes which release a variety of chemical mediators, including tumor necrosis factor alpha(TNFa), interleukin-8 (IL8), and leukotriene B4 (LTB4). respiratory tissue inflammation results in vasodilation, congestion, mucosal edema and globlet cells hypertrophy. These events trigger globlet cell production of excessive amount of mucus.
- 16. Pathophysiology; Chronic Bronchitis Changes in tissues include increased smooth muscle cartilage atrophy, infiltration of neutrophils and other cells and impairment of the cilia. Normally sterile airways become colonized with strep. Pneumoniae, H. influenza, RSV, Moraxella catarrhalis and mycoplasma species, Recurrent infections (viral and bacterial) reduce ciliary and phagocytic activity, increase mucus accumulation, weaken the body’s defenses and further destroy small bronchioles.
- 17. Pathophysiology; Chronic Bronchitis The airway degenerate and overall gas exchange is impaired, causing exertional dypnea. Hypoxemia results in increasing PaC02. If this is sustained, the brain’s respiratory control center and central chemoreceptor are desensitized and compensatory action to correct hypoxemia does not occur.
- 18. Pathophysiology; Emphysema anatomical changes of airways because of the loss of tissue elasticity. Inflammation and excessive mucus secretion cause airway trapping in the alveoli. This contributes to breakdown of the bronchioles, alveolar walls and connective tissue. Clusters of alveoli merge and the number of alveoli diminishes, leading to increased space available for air trapping.
- 19. Pathophysiology; Emphysema Destruction of airway walls causes collapse of small airways on exhalation and disruption of pulmonary capillary bed. Hypercapnea and respiratory acidosis are uncommon in emphysema because breathing imbalance is compensated for by increased in respiratory rate
- 20. Clinical assessment Chronic bronchitis typically has an insidious onset after age 45 Emphysema usually seen in the 50’s Chronic productive cough is the hallmark of chronic bronchitis. Dyspnea, lung infiltration, increased respiratory effort, altered breathing patterns, abnormal breath sounds including wheezing and diminished breath sounds. Progressive and incomplete airflow obstruction.
- 21. Laboratory Test. chest X-ray PFT ( assess pre and post bronchidilators) – decreased FEV1 and FVC ABG – hypoxemia, hypercarbia and acidemia Hct/Hgb – erythrocytosis ECG-RVH Cultures
- 22. Classification of COPD by severity. Stage Lung Function Stage 1: Mild COPD FEV1/FVC < 70% FEV1 > 80% predicated Stage 2: Moderate COPD FEV1/FVC < 50 - 70% FEV1 < 80% predicated Stage 3 Severe COPD FEV1/FVC < 30 - 70% FEV1 < 50% of pred. Stage 4: Very Severe COPD FEV1/FVC < 70% FEV1 < 3 0% predicated or FEV1 is < 50% predicated and respiratory failure
- 23. Differentiating Characteristics Chronic Bronchitis Emphysema Overweight (blue bloater) Thin (pink puffer) Mild Dyspnea Severe Dyspnea Copious Sputum Scanty Sputum Frequent Infections Less frequent Infections Hypoxemia Hypoxemia uncommon Barrel chest Flattened Diaphragm Cor pulmonale Diffusion capacity decreased
- 24. Factors Determining Severity of Chronic COPD. Severity of symptoms Severity of airway limitation Frequency and severity of exacerbations Presence of complications of COPD Presence of respiratory insufficiency Comorbidity General health status Number of medications needed to manage the disease
- 25. Components of COPD Management. Assess and monitor disease Reduce risk factors Manage stable COPD -Education -Non-pharmacologic -Pharmacologic Manage exacerbation
- 26. Goals of Therapy induce bronchodilation facilitate expectoration limit the impact of the disease on daily activities prevent complications smoking cession and avoidance of irritants
- 27. Goals of Therapy control life threatening disease exacerbations prevent complications teach patients about disease and the use of medications and improve therapeutic compliance
- 28. Non-Pharmacological Management. (NPT) Discontinue smoking Chest Physiology Breathing exercises Rehabilitation Preventative measures.
- 29. Discontinue Smoking most effective strategy to reduce the risk of developing COPD and affect the long-term rate of decline in FEV1. Group therapy Drugs (Chantrix; varenicline), nicotine replacement. Hypnosis
- 30. Chest Physiology Postural drainage Chest percussion and vibration Use if > 30 cc sputum/day
- 31. Breathing Exercises Inspire slowly and expire through pursed lips Inspiratory muscle training Breathing retraining
- 32. Rehabilitation Exercise reconditioning – increase endurance, exercise tolerance, maximal oxygen consumption Energy conservation Nutrition Psychosocial management – anxiety, depression and problems with cognitive perceptual and motor activity; financial and social resources
- 33. Preventative Measures Vaccines – annual influenza vaccine. Protection rate is 60-80 % Pneumococcal vaccine – recommended for patients with COPD, revaccination for patients>65 years if vaccination is >5 years Amantadine – efficacy is 50-90% 100mg bid for ages < 65mg. 100mg/day for ages > 65 years. Useful in non-immunized but exposed patients
- 34. Pharmacological Management of COPD Oxygen Anticholinergics Short acting Beta Agonists (SABA) Long Acting Beta Agonist (LABA) Combination therapy (CT) Theophylline Oral Steroids Inhaled steroids (IC) Antibiotics
- 35. Oxygen Therapy Administration of oxygen has been shown to increase survival and improve QOL. Oxygen can reverse hypoxemia, increase body weight, ameliorate right heart failure and improve exercise tolerance.
- 36. Oxygen Therapy Oxygen is needed for: Pt with PaO2 is < 55mmHg or Sa02 < 88% Pt with cor pulmonale or CHF (PaO2 is < 55mmHg or Sa02 < 89%) FEV1/FVC<70%; FEV1 <30% or presence of chronic respiratory failure or right heart failure. Specific situations: lung disease e.g. sleep apnea with nocturnal symptoms not corrected by continuous positive airway pressure
- 37. Anticholinergics (e.g. Ipratropium Bromide, Atropine, Glycopyrrolate, Tiotropium bromide Considered 1st line bronchodilators in the treatment of COPD COPD patients are very responsiveness to anticholinergics. Studies have shown equivalent and in some cases more effective than beta agonists in patients with chronic bronchitis and emphysema. Generally safe with less cardiovascular S/Es than high doses of beta agonists
- 38. MOA Ipratropium and atropine produce bronchodilation by competitively inhibiting cholinergic responses. They inhibit cyclic guanosine monophosphate leading to relaxation of bronchial smooth muscles Ipratropium also reduces sputum volume without altering viscosity Onset of action is 15mins (vs 5 mins for SABB ; peaks in 60-90 mins, has 6 hrs duration.
- 39. MOA Tiotropium is a long acting agent that protects against bronchoconstriction for >24hours. Onset is 30 mins; peak is 3 hours. It blocks M1, M2 & M3 receptors but dissociates quickly from M2 which may be responsible for rebound bronchoconstriction through the release of acethylcholine. Ipatropium in contrast binds to M3 over a prolonged period. It is delivered in a handihaler, a single load dry-powdered, breath activated device
- 40. Dosing Ipratropium MDI – 2 inhalations (40 mcg) qid. May be increased to 6 inhalations qid daily. Use spacer with closed mouth technique. Ipratropium Solution – 500mcg/2.5ml or more via nebulizer qid Tiotropium; the recommended dose is the inhalation of the contents of one capsule once daily using the handihaler. It is well tolerated with dry mouth the most common side effect.
- 41. Short acting Beta Agonist (salbutamol, albuterol Symptomatic benefits, but not as marked as obtained in asthma Reserved for prn use Inhaled agents preferred Can be used to assess/monitor patient’s current therapy Use to determine reversibility on spirometry S/Es generally seen with high doses (include palpitation, shakiness
- 42. MOA / DOSE cause bronchodilation of bronchial smooth muscles. May increase mucociliary clearance by stimulating ciliary activity Dose: MDI 2-4 puffs q 20 mins for up to 4 hours, then every 4 hours as needed. Nebulization; 2.5mg diluted to a total of 3ml, 3-4 times/day over 5-15 minutes.
- 43. Long Acting Beta Agonist; (salmeterol, formeterol) approved for use in COPD since 1997 have positive effect on QOL (one inhalation bid dosing) used as an add-on therapy where combination bronchodilator therapy is not adequate, patients with night time symptoms or patients with difficulty complying. Slow onset of action and expensive
- 44. Combination Therapy ( Ipatropium/Albuterol) The combination ofan inhaled anticholinergic &beta 2 agonist often is used as the disease progresses and symptoms worsen over time. Combination of bronchodilators with different MOA allows lowest effective doses to be used and reduces side effects. Superior to either albuterol or Ipratropium alone. more convenient but harder to adjust therapy.
- 45. Theophylline 2nd or 3rd line therapy potential action include: bronchodilation increase mucocillary clearance increase respiratory drive (effective short term) improved cardiovascular function – increase RVEF and LVEF increase diaphragmatic contractility improve exercise capacity
- 46. Dosing Acceptable plasma concentration is 8 - 12 mcg/ml and maximized if necessary up to 20mcg/ml Determine plasma concentration prior to dosing LD 3mg/kg aminophylline if prior theophylline within last 24 hrs and 6 mg/kg if none, given over 30mins Maintenance infusion of 0.4 mg/kg/hr Precautions: multiple S/Es, altered metabolism (smokers, CHF, elderly, liver disease), a lot of drug interactions.
- 47. Oral Steroids Only about 10% of patients benefit from oral steroids and there is high risk of dependence and side effects Can be used long –term if an objective benefit is seen after adequate trial – Prednisone 30mg qd x 2 weeks or more Some studies show that 50% of patients responding to oral steroids will respond to inhaled steroids. IV Methylprednisolone 50-100 mg q6-8h can be used in acute exacerbations. Taper as rapidly as possible
- 48. Inhaled steroids appropriate for symptomatic COPD patients with FEV1 < 50% predicted (stage 3 and stage 4) and repeated exacerbations treatment has been shown to reduce frequency of exacerbations and improve health status.
- 49. Antibiotics indicated if purulent sputum, infiltrates on chest x-ray or positive gram stain (usually pneumococcus or H. influenza) should be initiated within 24 hours of symptoms goal of therapy is to shorten the duration of exacerbations and prevent deterioration
- 50. Antibiotics Empirically treat for H. influenza (59%), S pneumoniae (17%) and M Catarrhalis (12%) Alternatives: Amoxicillin, Cephalosporins or TMX/SMX or Ampicillin Macrolides are also good but more expensive Treat for 7-10 days
- 51. Summary of Therapy by Stage.
- 52. Measure of Drug Effects Physiologic outcomes FT – airflow, gas exchange (ABG), diffusion Respiratory work – minute ventilation, spirometry. Symptomatic Outcomes – patient or physician assessment Dyspnea Functional Outcomes exercise tolerance work capacity – oxygen consumption 12 minutes walking test
- 53. Measure of Drug Effects Hospitalization Other Considerations stability of disease and response to therapy. airflow changes are not always closely correlated with exercise capacity.
- 54. Monitoring for Efficacy Parameter Range Frequency FEV1 Stable/ slowed Baseline and q2mths decline Sputum Decreased/ Continuous Production None Dyspnea Decreased Continuous Exacerbations Decreased Continuous
- 55. Monitoring for Toxicity Parameter Range Frequency FEV1 increasing Baseline and after 2 months FEV1/FVC decreasing Baseline & after 2 months
- 56. Role of the Pharmacist in the management of COPD. Pharmacist have a tremendous opportunity to identify patients at risk for COPD and to recommend for referral and assessment. Active promotion of activities aimed at smoking cessation is by far the most significant step a pharmacist can take. Patient education aimed at slowing the progress of the disease and improving compliance.
- 57. Role of the Pharmacist in the management of COPD. Too promote pharmacist/ patient interaction to empower the patient and improve patient self-management. Assess and make recommendation for drug therapy based on most current guidelines and literature.
- 58. Complications of COPD Pulmonary Hypertension Acute Respiratory Failure Infections Polycethemia.
- 59. Take Home Points/ Summary. COPD is a preventable disease that can be managed to reduce exacerbations and improve QOL for patients. It is a progressive generally irreversible inflammatory lung disease. It includes chronic bronchitis, emphysemia and less significantly, chronic asthma. Smoking is the major risk factor worldwide.
- 60. Take Home Points/ Summary. COPD is staged according to lung function. A definitive diagnosed is made by spirometry. Hallmark is FEV1/FVC ratio<70%. A major goal of therapy is symptom improvement and a reduction in the rate of FEV1 decline. Mild COPD maybe treated with NPT + SABA. Moderate COPD add LABA and/or CT.
- 61. Take Home Points/ Summary. Severe COPD add IC if repeated exacerbations. Oral steroids show little benefit and increases toxicity. Chronic use should be avoided. Long term Oxygen therapy is given in cases of acute respiratory failure. The Pharmacist has an important role in the management of COPD; to educate, to prevent exacerbations, hospitalization, development of respiratory failure and death.
- 62. References Talbert, Robert L. Ischemic Heart Disease In: Di Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. NY: McGraw Hill; 2005: 271-277. Budeus M, Hennersdorf M, Perings S, et al. Amiodarone prophylaxis for atrial fibrillation of high-risk patients after coronary bypass grafting: a prospective, double-blinded, placebo-controlled, randomized study. Eur Heart J . 2006 Jul;27(13):1584-91. Kerstein J, Soodan A, Qamar M, et al. Giving IV and oral amiodarone perioperatively for the prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass surgery: the GAP study. Chest . 2004 Sep;126(3):662-4. Leavitt BJ, Ross CS, Spence B, et al. Long-term survival of patients with chronic obstructive pulmonary disease undergoing coronary artery bypass surgery. Circulation . 2006 Jul 4;114(1 Suppl):I430-4. ACC/AHA/ESC Practice Guidelines Circulation. 2006;114:700-752 Respiratory Care Web ED Accessed at: classes.kumc.edu/cahe/respcared/cybercas/cabg2/stevobj.html
Editor's Notes
- #56: Students to fill in toxicities.